Immunogenicity of biotherapeutics is indispensable for drug master files. Drug MOAs is the prerequisite for cell based NAb assay, while idea cell potency assays are not necessarily suitable for NAb assays because NAb itself can bind certain cell surface proteins, such as FcγRs, thereby inducing non-specific antibody dependent cellular cytotoxicity. Thus, it is demanding to have the cellular protein expression data to build cell models. Large scale omics data, including CCLE and HCA, can be leveraged to have the detailed cellular protein expression data especially for cell surface protein prior to setting up cellular models. However, given that the widely available mRNA expression data cannot be used to surrogate protein expression, we have been building an infrastructure to aligning cell models with drug MOAs aided by multiple-omics data analysis. We have been streamlining this pipeline with accomplishments of NAb assays for clinical trials of ADCs, GLP-1, Cytokine mutein drugs.
Learning Objectives:
CCLE and HCA introduction
Antibody dependent cellular cytotoxicity.
Inferring protein expression from mRNA expression via statistical learning and generative AI from OMICs data.
